1- Methoxybutadiene

Woodward and Hoffmann pointed out that the Diels-Alder reaction involved bonding overlap of the highest-occupied molecular orbital (HOMO) on the diene and the lowest-unoccupied molecular orbital (LUMO) on the dienophile. Display the HOMO for 2-methoxybutadiene. Where is it localized Display the LUMO for acrylonitrile. Where is it localized Orient the two fragments such that the HOMO and LUMO best overlap (A clearer picture is provided by examining-the HOMO map for 2-methoxybutadiene and the LUMO map for acrylonitrile.) Which product should result ... 

Examine transition states leading to para and meta adducts 2-methoxybutadiene+acrylonitrile para and meta) as well as the adducts themselves (l-methoxy-4-cyanocyclohexene and l-methoxy-5-cyanocyclohexene). What should the kinetic product be Is this in line with your expectations based on orbital interactions Is this also the thermodynamic product ... 

HOMO map for 2-methoxybutadiene reveals (in blue) where the HOMO is concentrated on the exposed electron density surface. 

In addition, the scope of this methodology was extended to the involvement of other bis(sulfonamides) ligands, acyclic dienes such as 2-methoxybutadiene... 

Scheme 5.22 Al-catalysed Diels-Alder reactions between 2-methoxybutadiene and A -arylmaleimides with bis(sulfonamides) ligands.

The ketene 37 reacjs with 2-methoxybutadiene to afford a 63% yield of the rearranged methylenedihydropyran 38 (equation 22)24. In contrast, dimethylketene and 1-methoxy-butadiene form a normal cycloadduct , the cyclobutanone 39 (equation 23)24. 

Anthracyclinones The anthraquinone 1, available from the commercial dyestuff l,4,5-trihydroxy-9,10-anthraquinone, reacts regiospecifically because of the halo substituent with 2-methoxybutadiene to give 2. The product can be converted by ketalization and oxidation into the quinone 3, a known precursor to anthracyclinones. 

Chiral (.S, .S )-diazaaluminolidine catalyst brought about the first highly enantioselective catalytic Diels-Alder reaction of an achiral C2v-symmetric dienophile with an achiral diene. Addition of 2-methoxybutadiene to A-o-tolylmaleimide in the presence of 20 mol % (5,5)-diazaaluminolidine gave rise to the cycloadduct in 98% yield and 93% ee one recrystallization from i-PrOH-hexane furnished the enantiomerically pure compound [57] (Eq. 8A.34). The Diels-Alder reaction of 2-((trimethylsilyl)methyl)butadiene and A-aryimaleimide promoted by this catalyst has been successfully applied to the enantioselective total synthesis of Gracilins B and C [58],... 

Example. We will look at the reaction between 2-methoxybutadiene and methyl acrylate. The frontier orbital energies and coefficients at the reactive sites are... 

P1D and P4/D have non-negligible values if a donor is present in the 2-position, because 4 1 and 4 have significant coefficients at this site. As a consequence, every 4t orbital contributes to the HOMO (see scheme e below). The coefficients at the central carbons are difficult to evaluate because some of the contributions cancel, but there is no doubt that the coefficient at C4 is much greater than that at C4. Catalog examples are isoprene and 2-amino- and 2-methoxybutadiene. 

Methoxybutadiene can be used to model the diene in a qualitative treatment. AMI calculations give very similar S and C LUMO coefficients for 0=CH—CH=S however, the difference is more pronounced in STO-3G and 3-21G calculations. Note that even with AMI calculations (C coefficient = —0.64 S coefficient = 0.65), a preference is still expected for attack at sulfur, as sulfur orbitals are much more diffuse than carbon orbitals (covalent radii 1.02 and 0.77 A respectively). 

The Rates of Diels-Alder Reactions. Most Diels-Alder reactions require that the dienophile carries a Z-substituent before they take place at a reasonable rate. Butadiene 6.144 will react with ethylene, but it needs a temperature of 165 °C and high pressure, whereas the reaction with acrolein is faster, taking less time at a lower temperature. An X-substituent on the diene, on C-l or C-2, increases the rate further, with 1-methoxybutadiene 6.145 and 2-methoxybutadiene 6.146 reacting with acrolein at lower temperatures. Times and temperatures are not a reliable way of measuring relative rates, but these four reactions were taken to the point where the yields of isolated product are close to 80%. 

Methoxybutadienes. These dienes can be obtained by alkylation of the anion of methoxyallene followed by isomerization to the diene with pyridinium tosylate. Other acid catalysts are not useful. The (E)-isomer of the diene is formed predominantly or exclusively. 

The first example of an asymmetric Diels-Alder reaction of a maleimide was reported by Corey, Sarshar, and Lee, who used the same catalyst system [59], The catalyst and maleimide were optimized for the cycloaddition with 2-methoxybutadiene as shown in Sch. 34. For high asymmetric induction it was found that that 3,5-dimethyl substituents... 

Stereospecificity, the property that the stereochemistry of the starting materials determines the stereochemistry of the product, is one of the hallmarks of pericyclic reactions. It is possible to draw two-step nonconcerted, polar or free-radical mechanisms for many pericyclic reactions, but these two-step mechanisms fail to account for the stereospecificity of the reactions. For example, a two-step polar mechanism can be drawn for the Diels-Alder reaction between 2-methoxybutadiene (a nucleophile) and ethyl cA-crotonatc (an electrophile). This mechanism proceeds through a dipolar intermediate in which one new cr bond has formed. In this intermediate, there is free rotation about the two C atoms of the dienophile, so the cis stereochemical relationship between the Me and CC Et groups is expected to be lost in the product. In fact, though, the product is exclusively cis. This finding does not completely rule out a polar mechanism— it is possible that the intermediate exists but that ring closure occurs more quickly than rotation about the cr bond—but it does limit the lifetime of the dipolar intermediate to such an extent that one can say practically that it does not exist. 

The allyl vinyl ethers are usually prepared in situ, but it is also possible to isolate the primarily formed mixed acetals or allyl vinyl ethers155-1 57. With low-boiling vinyl ethers the reaction is carried out in a sealed tube with an excess of the vinyl ether. For a tandem Claisen-rearrangc-ment-ene cyclization involving the Saucy-Marbet reaction cf. ref 158. The generation of isopropenyl ethers from esters is described in ref 159. For a related Claisen rearrangement by the reaction of 2-methoxybutadiene with ends and phenols see ref 160. 

Alkoxychromans. A tube containing o-cresol, 2-methoxybutadiene, and dry benzene sealed under vacuum, and heated 21 hrs. at 160° 2,8-... 

A mixture of dimedone, 2-methoxybutadiene, and benzene refluxed 16.5 hrs. 5,5-dimethyl-2-(3-methoxy-2-butenyl)cyclohexane-l,3-dione. 

A mixture of acrolein, 2-methoxybutadiene, benzene, and some hydroquinone heated 30 min. at 160° in a stainless steel bomb -> 4-methoxy-3-cyclohexene-l-carboxaldehyde (startg. m. f. 235). Y 75%.— Tbe reaction gives a single isomer. J. I. DeGraw, L. Goodman, and B. R. Baker, J. Org. Chem. 26, 1156 (1961). 

Methoxybutadiene reacts with diphenyl- and butylethylketene to give the [4+2] cycloadducts... 

The difference in reactivity between aldehyde and ketone groups is illustrated by the Diels-Alder adduct between acrolein and 2-methoxybutadiene (5) which on treatment with methanol and ammonium chloride gives the keto-acetal (6) [39], while... 

Condensations of Nonaromatic Dienes. Of bicyclic dienic compounds with a cis-linkage of rings A and B, cis-l-vinyl-9-methyl-A -6-octalone (225) has been studied in the greatest detail. The synthesis of this diene was effected in four stages via the acetylenic carbinol (224) from the methoxyketone (223), obtained in its turn with a yield of about 50% by the diene condensation of 2-methoxybutadiene with 2-methylcyclohex-l-en-3-one [323, 330, 335] (Scheme 21). In the condensation of the dienone (225) with 2,5-dimethylcyclopent-l-en-3-one, eight racemic adducts are theoreti-... 

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